Actions of the opioid antagonist, nalmefene, and congeners on reperfusion cardiac arrhythmias and regional left coronary blood flow.
Opioid antagonists have been shown to prevent the occurrence of lethal arrhythmias following coronary reperfusion. In this study, we have examined the effect of a new, long-lasting, potent opioid antagonist, nalmefene, and congeners in the prevention of reperfusion arrhythmias in dogs. Nalmefene given at a dose of 1 mg/kg i.v. reduced the incidence of reperfusion arrhythmias significantly when compared to the saline control. Neither N-methyl nalmefene, a quaternary analog that does not cross the blood brain barrier, nor (+) nalmefene, an isomer with no anti-opioid actions, provided any protection against reperfusion arrhythmias. Regional myocardial blood flow profiles, during and after coronary occlusion, were not different between the nalmefene- and saline-treated groups. We conclude that nalmefene prevents the occurrence of reperfusion-induced arrhythmias by blocking opioid receptors in the brain.
Caldwell
R W
RW
Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta.
Nagarajan
R
R
Chryssanthis
A
A
Tuttle
R R
RR
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000517:prevention & control*; D003326:Coronary Circulation / Q000187:drug effects; D004285:Dogs; D005260:Female; D007275:Injections, Intravenous; D008297:Male; D015425:Myocardial Reperfusion / Q000009:adverse effects*; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology*; D011292:Premedication; D013997:Time Factors; D016277:Ventricular Function, Left / Q000187:drug effects
D009292:Narcotic Antagonists; D009271:Naltrexone; C038981:nalmefene